Over the last decades intensive selection on growth rate has been done in broiler chicken strains developed for meat production. However, fatness has also been increased, leading to excessive adiposity. By reducing feed efficiency and lean meat yield, this excess of fat tissue is a major drawback for production.
In order to decipher the metabolic and genetic mechanisms involved in the regulation of fatness in the chicken, some investigators have developed experimental models of adiposity. Lean and fat chicken lines have been divergently selected from adipose tissue weight (Leclerq et al., 1980) and for very low density lipoprotein (VLDL) plasma concentration (Whitehead, C. C., Griffin, H. D., 1984). Studies performed in lean and fat lines developed by Leclercq et al (1980) indicate that the difference in adiposity between lines was not the result of a difference in food consumption or in nutrient utilization. Stearoyl-Co-A desaturase activity and plasma VLDL concentration were found to be higher in the fat line (Legrand, P. and Hermier, D., 1992), suggesting a higher lipogenesis rate in this line.
In the chicken, lipogenesis occurs essentially in the liver, the adipose tissue being only a storage tissue (O'Hea, E. K. and Leveille, G. A., 1968; Griffin et al., 1992).
The Spot 14 gene, also referred to as thyroid hormone responsive Spot 14 protein (THRSP), encodes a small acidic protein that was discovered in earlier studies of thyroid hormone action on hepatocytes (Seelig et al., 1981; Jump et al., 1984; Liaw and Towle, 1984). Although the exact molecular mechanism is not clear, THRSP is strongly implicated as a transcription factor that controls expression of major lipogenic enzymes. For instance, THRSP is only expressed in lipogenic tissue such as liver, fat and the mammary gland (Liaw and Towle, 1984; Jump and Oppenheimer, 1985). THRSP mRNA levels are greatly increased by carbohydrate feeding or insulin-injection and decreased by high plasma glucagon levels or by feeding a diet rich in polyunsaturated fatty acids (Jump et al., 1993). Hepatocytes transfected with a THRSP antisense oligonucleotide express decreased mRNA levels in enzymes involved in the lipogenic pathway [i.e., ATP-citrate lyase (ACLY), fatty acid synthase (FAS) and malic enzyme (ME)] (Kinlaw et al., 1995; Brown et al., 1997). Although an increase in lipogenesis was observed in the THRSP knockout mouse, this contradiction could be due to incomplete gene deletion or overcompensation by alternative pathways (Zhu et al., 2001). Homodimers of THRSP interact with and activate chicken ovalbumin upstream promoter-transcription factor 1 (COUP-TF1) in promoting transcription of L-type pyruvate kinase (L-PK) through an interaction with specificity protein 1 (Spl) (Compe et al., 2001). Furthermore, the THRSP promoter region contains three thyroid response elements (TREs) that work synergistically and interact with far upstream region (FUR) elements to maximize triuodothyronine (T3) responses in hepatocytes (Liu and Towle, 1994). Apparently, the human THRSP promoter responds more robustly to T3 than glucose, while the rat THRSP promoter region is more responsive to glucose than T3 (Campbell et al, 2003).
Many common diseases and conditions are not caused by a genetic variation within a single gene, but are influenced by complex interactions among multiple genes as well as environmental and lifestyle factors. Genetic predisposition is the potential of an individual to develop a disease or condition based on genes and hereditary factors. Although both environmental and lifestyle factors add tremendously to the uncertainty of developing a disease, it is currently difficult to measure and evaluate their overall effect on a disease process. By studying changes within a gene that have been found to be associated with a disease trait, researchers may begin to reveal relevant genes associated with a disease. Polymorphisms can thus serve as biological markers for a disease or trait associated with a disease. Therefore, it is desirable to find polymorphism(s) which can be used for the diagnosis of a disease (including metabolic diseases such as obesity) and/or identification of a trait, such as polymorphisms associated with a fat or lean chicken phenotype.